Improving Proteomic Dynamic Range with Multiple Accumulation Precursor Mass Spectrometry

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Proteomics

Background:

• Orbitrap (OT)-based mass spectrometers are crucial for high-resolution analysis but suffer from slower scanning speeds compared to other mass analyzers.
• Extending the dynamic range of precursor ion detection is essential for comprehensive analysis in mass spectrometry.
• Current methods often require complex software or hardware modifications to improve performance.

Purpose of the Study:

• To enhance the precursor dynamic range of Orbitrap mass spectrometers without requiring hardware or software modifications.
• To introduce and evaluate a novel method called multiple accumulation precursor mass spectrometry (MAP-MS).
• To assess the impact of MAP-MS on both data-dependent acquisition (DDA) and data-independent acquisition (DIA) methods.

Main Methods:

• Utilized long Orbitrap (OT) transients to extend precursor dynamic range.
• Modified the selected ion monitoring method to multiplex several precursor m/z ranges into a single scan, termed multiple accumulation precursor mass spectrometry (MAP-MS).
• Collected data using both data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies for evaluation.

Main Results:

• MAP-MS achieved nearly 2x increase in precursor dynamic range with no significant consequences or additional ion accumulation time.
• Precursor quantification improved with higher quality measurements when using MAP-MS in DDA mode.
• Peptide detection in DIA mode was enhanced by up to 11% when combining precursor and tandem mass spectra with MAP-MS.

Conclusions:

• Multiple accumulation precursor mass spectrometry (MAP-MS) is an effective, modification-free strategy to significantly enhance precursor dynamic range in Orbitrap mass spectrometry.
• MAP-MS improves quantitative accuracy in DDA and boosts peptide detection sensitivity in DIA, offering broad applicability.
• This approach represents a valuable advancement for high-resolution mass spectrometry, particularly in complex biological sample analysis.